Radiation Force Imaging of Prostate Cancer and Guidance of Biopsy Procedures

前列腺癌的辐射力成像和活检程序指导

• 批准号: 7768872
• 负责人: Kathryn Radabaugh Nightingale
• 金额: $ 40.51万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-18 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7768872
• 关键词: Acoustics; Adenocarcinoma; Algorithms; Ally; Benign; Benign Prostatic Hypertrophy; Biopsy; Breast; Cancer Detection; Cardiovascular system; Cessation of life; Characteristics; Clinical; Cold Therapy; Core Biopsy; Coupled; Cutaneous; Data; Detection; Development; Diagnosis; Digital Rectal Examination; Disease; Elasticity; Europe; Gleason Grade for Prostate Cancer; Goals; Growth; Hand; Heating; Histologic; Histology; Histopathologic Grade; Image; Imagery; In Situ; Inflammation; Investigation; Laboratories; Lesion; Liver; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Methods; Monitor; Needles; Newly Diagnosed; Pathologic; Pathology; Patient observation; Pattern; Physiologic pulse; Procedures; Process; Prostate; Prostate Cancer therapy; Prostate-Specific Antigen; Prostatic; Radiation; Radiation therapy; Radical Prostatectomy; Recurrence; Reporting; Research; Resolution; Sampling; Screening procedure; Specimen; Staging; Stress; Structure; System; Thyroid Gland; Time; Tissues; Transducers; Tumor Tissue; Ultrasonic Diagnosis; Ultrasonic Transducer; Ultrasonics; Ultrasonography; United States; Universities; Work; base; cancer recurrence; clinical application; clinically significant; cohort; density; design; imaging modality; improved; in vivo; men; public health relevance; response; standard of care; tumor

DESCRIPTION (provided by applicant): Prostate cancer (PCa) is the most common non-cutaneous cancer in men in the United States, with over 185,000 cases newly diagnosed, and over 28,000 deaths annually [1, 2]. Screening methods are now widely used in the United States and Europe to detect PCa, which include digital rectal examination (DRE), and prostate-specific antigen (PSA) analysis. When suspicion is raised through these screening mechanisms, prostate biopsies are performed to diagnose PCa, which depends upon the presence of adenocarcinoma in biopsy cores, with clinical significance being determined by the presence of 50% or more PCa tumor tissue in 3 or more biopsy cores, a Gleason sum (GS, histologic analysis) greater than 6, and a PSA density (PSA divided by ultrasound derived volume of prostate) more than 0.15[3]. The clinical standard for performing prostate biopsy is ultrasound-guided, transrectal, laterally directed 18G needle cores, with the number of cores ranging from 6-12, systematically sampling different regions of the prostate[4]. This standard does not involve targeting needles to suspicious regions since PCa does not have unique B-mode ultrasound image characteristics that can delineate diseased from normal structures and benign pathologies of the prostate (e.g., benign prostatic hyperplasia (BPH) and inflammation). The current standard of care has a dismal sensitivity (only 53% using octant systematic biopsy in a cohort of radical prostatectomy specimens with previously diagnosed, clinically significant disease, [5]), mainly because the sampling grid only randomly intersects the pathologic tissues. Over 1,000,000 prostate biopsies are performed annually in the United States[6], with PCa detection rates being low (25-36%)[6]. PCa detection rates on repeat biopsies (cases with negative first biopsies) are again 10-35% [7, 8]. The fact that these rates are identical suggests that as many cancers are detected as are missed during a single systematic biopsy session. In addition, many of the cancers that are detected with this approach are clinically insignificant[3]. Elastography imaging methods have shown promise for PCa visualization and prostate biopsy guidance based upon stiffness differences between normal and pathologic tissues[9]. However, elastography methods can be limited by an inability to apply uniform compression (stress) to the prostate using a hand-held transrectal ultrasonic transducer. Acoustic Radiation Force Impulse (ARFI) imaging is an elastography imaging method that we have developed at Duke University that overcomes these challenges through the use of focused acoustic beams for the application of stress. We have obtained promising initial ex vivo and in vivo results, in which normal prostatic structures and focal PCa lesions are clearly visualized in ARFI images that are not visualized in matched B-mode images. The in vivo data demonstrate a clear advantage of ARFI imaging over conventional elastography for PCa visualization, in that the acoustic energy is coupled directly into the prostate. We propose to develop and optimize dedicated 2D and 3D transrectal in vivo ARFI imaging methods for the purpose of visualizing PCa and differentiating PCa from benign processes in the prostate; to evaluate the correlation between suspicious regions in ARFI images and tissue histology, to investigate the correlation between local PCa Gleason pattern (measure of histologic aggressiveness) and PCa visibility in ARFI images, and to evaluate the potential increase in biopsy detection rate of clinically significant PCa under ARFI image guidance. If successful, this research has the potential to greatly improve cancer detection rates for clinically significant grade PCa (i.e. GS 7 or more) during first time biopsies, to reduce the number of biopsy cores taken during biopsy, to facilitate longitudinal monitoring of PCa growth or recurrence after in situ therapies, and to provide image guidance for focal PCa therapies. PUBLIC HEALTH RELEVANCE: Prostate cancer (PCa) is the most common non-cutaneous cancer in men in the United States, with over 185,000 cases newly diagnosed, and over 28,000 deaths annually [1]; PCa is currently diagnosed by ultrasonic guided biopsy in which systematic sampling of the prostate is performed because PCa is not generally visualized in ultrasonic images, thus, PCa biopsy is reported to have poor sensitivity (53%)[5]. We propose to develop ultrasonic radiation force based stiffness imaging methods capable of visualizing focal cancers in the prostate, thus providing targeting for biopsy procedures. If successful, this research has the potential to greatly improve the cancer detection yield for clinically significant grade cancers on first time biopsies, to reduce the number of biopsy cores taken during biopsy, to facilitate longitudinal monitoring of PCa growth or recurrence after in situ therapies, and to provide image guidance for focal PCa therapies.

描述（由申请人提供）：前列腺癌（PCa）是美国男性中最常见的非皮肤癌，每年新诊断超过185，000例，死亡超过28，000例[1，2]。筛查方法目前在美国和欧洲广泛用于检测PCa，包括直肠指检（DRE）和前列腺特异性抗原（PSA）分析。当通过这些筛选机制引起怀疑时，进行前列腺活检以诊断PCa，这取决于活检芯中腺癌的存在，临床意义通过在3个或更多个活检芯中存在50%或更多的PCa肿瘤组织来确定，Gleason总和（GS，组织学分析）大于6，PSA密度（PSA除以超声导出的前列腺体积）大于0.15[3]。进行前列腺活检的临床标准是超声引导、经直肠、侧向定向的18 G针芯，针芯数量范围为6-12，系统地对前列腺的不同区域进行采样[4]。该标准不涉及将针靶向可疑区域，因为PCa不具有可以从前列腺的正常结构和良性病变（例如，良性前列腺增生（BPH）和炎症）。目前的护理标准具有令人沮丧的灵敏度（在具有先前诊断的临床显著疾病的根治性直肠癌切除术样本队列中，使用八分法系统活检仅为53%[5]），主要是因为采样网格仅随机与病理组织相交。在美国，每年进行超过1，000，000次前列腺活检[6]，PCa检出率较低（25-36%）[6]。重复活检（首次活检阴性病例）的PCa检出率仍为10-35% [7，8]。这些比率相同的事实表明，在一次系统性活检过程中，检测到的癌症与遗漏的癌症一样多。此外，用这种方法检测到的许多癌症在临床上是不重要的[3]。弹性成像方法已显示出基于正常组织和病理组织之间的刚度差异的PCa可视化和前列腺活检引导的前景[9]。然而，弹性成像方法可能受到无法使用手持式经直肠超声换能器向前列腺施加均匀压缩（应力）的限制。声辐射力脉冲（ARFI）成像是我们在杜克大学开发的一种弹性成像方法，通过使用聚焦声束施加应力克服了这些挑战。我们已经获得了有希望的初步离体和体内结果，其中正常前列腺结构和局灶性PCa病变在ARFI图像中清晰可见，而在匹配的B型图像中则不可见。在体内的数据表明，ARFI成像的明显优势，在传统的弹性成像PCa可视化，在声能直接耦合到前列腺。我们建议开发和优化专用的2D和3D经直肠体内ARFI成像方法，用于可视化PCa并将PCa与前列腺中的良性过程区分开来;评估ARFI图像中可疑区域与组织学之间的相关性，研究局部PCa Gleason模式与组织学之间的相关性，（测量组织学侵袭性）和ARFI图像中PCa的可见性，并评估ARFI图像引导下临床显著PCa活检检出率的潜在增加。如果成功，该研究有可能大大提高首次活检期间临床显著等级PCa（即GS 7或以上）的癌症检出率，减少活检期间采集的活检芯数量，促进原位治疗后PCa生长或复发的纵向监测，并为局灶性PCa治疗提供图像指导。 公共卫生相关性：前列腺癌（PCa）是美国男性最常见的非皮肤癌，每年新诊断超过185，000例，死亡人数超过28，000人[1]; PCa目前通过超声引导活检来诊断，其中进行前列腺的系统采样，因为PCa通常在超声图像中不可见，因此，据报道，PCa活检的敏感性较差（53%）[5]。我们建议开发基于超声辐射力的刚度成像方法，能够可视化前列腺中的局灶性癌症，从而为活检程序提供靶向。如果成功的话，这项研究有可能大大提高首次活检时临床显著级别癌症的癌症检测率，减少活检期间采集的活检芯的数量，促进原位治疗后PCa生长或复发的纵向监测，并为局灶性PCa治疗提供图像指导。